Synthesis of optically active cis- and trans-1,2-disubstituted cyclopropane derivatives by the Simmons-Smith reaction of allyl alcohol derivatives derived from (R)-2,3-O-isopropylideneglyceraldehyde

Abstract

The Simmons-Smith reactions of Z- and E-allyl alcohol derivatives 6 derived from (R)-2,3-O-isopropylideneglyceraldehyde (6) were used for the synthesis of optically active cis- and trans-1,2-disubstituted cyclopropane derivatives. Reaction of 6 with diethyl zinc and diiodomethane gave cyclopropane derivatives 7 in 84% to quantitative yields with 35 to ≃100% des. Identical facial selectivities toward the double bonds, 1re-2si for Z-6 and 1re-2re for E-6, were observed in the cyclopropanations. The diastereoselectivity was dependent on the protecting group on the terminal allylic oxygen (R of 6, TBDPS>MOM>Bn) and on the stereochemistry of the double bond (Z >E). For TBDPS ethers Z-and E-6c, cis- and trans-7c were obtained as single distereomers, respectively. It was clearly demonstrated that the stereoselectivity of the cyclopropantion is controlled by the directing effect of the allylic oxygen (O-1) of the dioxolane ring, which coordinates to the reagent. The terminal allylic oxygen (O-2) lowered the diastereoselectivity. This reaction was applied to the synthesis of optically active cyclopropane analogs of γ-aminobutyric acid (GABA) 18,22, and ent-22